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1 Risk-Based cGMPs: Defining Risk and Quality April 22, 2003 Bruce Burlington

Risk-Based cGMPs: Defining Risk and Qualitypqri.org/wp-content/uploads/2015/08/pdf/RiskBased042203.pdf · Change the focus from controlling GMP requirements to controlling the “Risk

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Page 1: Risk-Based cGMPs: Defining Risk and Qualitypqri.org/wp-content/uploads/2015/08/pdf/RiskBased042203.pdf · Change the focus from controlling GMP requirements to controlling the “Risk

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Risk-Based cGMPs:Defining Risk and Quality

April 22, 2003Bruce Burlington

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Risk-Based Approach to cGMPs

PhRMA Welcomes the FDA’s Initiative

Science-based risk management & integrated quality systems cGMPs approach

Attention focused on control of critical manufacturing points that define quality

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Risk-Based Approach to cGMPs Task Force

Bruce Burlington Wyeth

Dave Haggard Merck

Ed Kaminski Wyeth

Frances Sakers Wyeth

John Grazal Astra Zeneca

Janice Whitaker GSK

Erika King PhRMA

Alice Till PhRMA

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Questions We Asked

1. What is the meaning of risk? 2. How do we maintain high quality standards?3. What regulations or practices are affected?4. What are the benefits to this new approach?5. How does industry collaborate with FDA Field and

Center Offices?6. How would this affect new technology?7. How does this fit with CMC and other initiatives?

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Task Force Approach

1. Define the Ideal State: Phase in changes2. Guiding principles – as we move forward:

Improve efficiency for both FDA and industry Identify the meaning and scope of “risk-based”Risk to whom? Patient centered: safety, efficacy,& availability

3. Identify additional benefits and behavioral changes

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Meaning and Scope of Risk-based

The focus must be from the patients viewpoint.We believe the patient wants pharmaceutical products to:1. Be available when needed2. Be “fit for use,” meaning

SafeEffectiveReadily identifiableConvenient to use

Quality can be defined as consistently and reliably meeting patient needs.

Safety and efficacy of the product for use relates to the product used to generate clinical data.

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Improve Efficiency

Efficient (and effective) GMPs allow focus on:Critical vs. non-critical parameters.Non-patient oriented controls may divert effort away from adequate drug product quality, availability and effective problem resolution.

Quality SystemsCritical Process ParametersCritical Control Points

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Additional Benefits

Unites the CMC submission and cGMPs on requirements, review and interpretation

Critical quality parameters and critical control points require special consideration (as opposed to non-critical parameters)

Provides a framework for product specific SUPAC

Assists in an equitable and consistent interpretation by both industry and FDA

eg. Technical dispute resolution process

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Behavioral Changes

Industry must provide full development reportsand design product quality into manufacturing and testing procedures.

FDA must focus on critical process and/or control parameters that may impact product safety and efficacy in NDA reviews and inspections.

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An Ideal State

A Paradigm Shift:Change the focus from controlling GMP requirements to controlling the “Risk to the Patient.”

The Challenge to FDA and Industry:Regulations must be compatible with satisfying patient requirements for safety, efficacy & availability.

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nReview each System (FDA Systems Based Inspection Program) using the Risk-Based GMP Framework.nReview GMP Framework in a risk-based environment.nReview Examples of current GMP activities of concern.

Tier 2: Acceleration

6-12 months

nOperational issues exist around the guidance documents themselves and the interpretation by FDA investigators. Many of the current guidance documents were not constructed with a consideration of risk models, e.g. High Purity Water Systems (1993) and Cleaning Process Validation (1993). All of the “Guide to Inspection of…”could be reviewed with an emphasis on considering risk (patient safety, use). Additionally, the actual field interpretation of the documents has been noted to go beyond the actual guidance. Specific examples of this could be provided. An emphasis could be on a negotiation process between the Center and the firm with science vs. compliance issues defaulting to science.

Tier 1: A Beginning6 months

FDA GMP Inspection Based IssuesTime Frames

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nThe current 21 CFR 210-11 is revised, retaining assurance the product is safe and efficacious.nThe NDA CMC section development report supports company’s risk management strategy.nIdentify the Risk level (low, medium, high) for probability and severity of impact on patient safety and efficacy,

o Critical Control Pointso Interim Specificationso Critical Process Parameterso Quality Systems

nThe amount and content of documentation to support each risk level is proportional to the risk level.nLow risk changes do not require supplements as long as the resultant change is still rated as low risk.nDocument and trend all data for an overall Annual Product Risk Review, on file and available for FDA inspections.nPAT, etc. – reduced or eliminated end product testing.

Tier 3: The Ideal

State1-3 years

FDA GMP Inspection Based IssuesTime Frames

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Next Steps for the Journey

The FDA and industry work in collaboration employingrisk-based management principles to:

Measure the significance of production issues against medical need and product availability.Guide in the implementation, review and application of technological advances.Scrutinize changes and the change approval process to allow for other means of pre-approval review.Appropriately target audit and inspection plans (duration and intensity) based on inherent risks of product/site compliance.